When Wynkoop arrived in Kansas and heard about Chivington's attack, he admittedly flew into a rage and accused Chivington of setting the Cheyennes up for the attack to bolster his military record, something that would surely propel Chivington's future political career. Wynkoop was further enraged when he learned that, at the time Chivington attacked the Indians at Sand Creek, his enlistment in the Army was expired and he led the Army- sanctioned volunteer militia with no official military authority. Alarmed by Wynkoop's accusations and the rumors of a wholesale massacre perpetrated by the militia, General Curtis ordered Wynkoop to return to Fort Lyon and conduct an investigation into the matter. Wynkoop received letters from Soule and Cramer, confirming the events that transpired at Sand Creek, and he interviewed other Lyon officers and enlisted men who told similar stories.

During the ensuing months, two more government investigations of the incident at Sand Creek were pressed in addition to the military tribunal presided over by Lt. Colonel Samuel Tappan (Tappan was a publicly avowed enemy of Chivington). Captain Soule was a star witness against Colonel Chivington at the military hearing in Denver, in which he gave damning testimony that the Indians at Sand Creek were indeed camped under the protection of the U.S. Army. Soule and other Fort Lyon officers also testified to witnessing several of Chivington’s volunteer militiamen engaged in subsequent visceral depredations. Soule, who in the interim had been transferred to the Denver Provost Guard, became the target of many Chivington supporters, and survived several murder attempts during the Denver hearings.

On April 23, 1865, Soule was lured into the streets of downtown Denver (approximately 14th and Arapahoe Street in present-day Denver), and murdered by Private Charles W. Squier, of the Second Colorado Cavalry, and an accomplice, William Morrow. Squier, who had earlier been accused of attempted murder of another Denverite but released on a jurisdictional technicality, fled the scene. He was later tracked down in New Mexico and brought back to face murder charges in Denver. Just days before his trial, however, Squier escaped from jail with the help of confederates and was never seen again. Although there was no evidence that Chivington had anything to do with Soule's murder, many Denver residents who once ardently supported the Fighting Parson suspected he was behind it. Grief-stricken over the death of his dear friend Soule, Wynkoop was Chivington's most vocal accuser.

Interestingly, the government in its investigations never questioned Soule or Cramer about their refusal to obey Chivington’s orders to attack the Indians at Sand Creek. In fact, neither officer was ever charged with any violation of military protocol. Some historians theorize that this fact, if it had been put in the official record, would have exposed the severe military breakdown at Sand Creek because Chivington's enlistment in the Army had technically expired two months prior to the attack. He had not, however, been replaced as Denver's military commander due his superior officer's more pressing concerns of the Civil War in the States. The government did, however, officially condemn Chivington and the misdeeds of his Colorado Third Volunteers, and promised reparations to the Sand Creek survivors that were only partially paid. By the time the investigations concluded, Chivington had finally mustered out of service and was immune to any military or civil prosecution, despite the government's hollow recommendation that he be charged with criminal conduct.

The personal pronoun “I” rarely found a comfortable place in Ned Wynkoop’s vocabulary. Indeed, the tall and imposing Pennsylvanian was impulsive, emotionally brash, easily agitated, and sometimes downright arrogant in his youth, but the young boy who always stepped in to stop a schoolyard brawl forever carried that most admirable quality of temperance throughout his life. He was the first to take responsibility for his mistakes, and although sometimes the proverbial bull in a china closet when it came to military protocol, Wynkoop impressed his superiors more often than confounded them. If nothing else, history will forever remember Ned Wynkoop as the consummate arbitrator with a keen insight to human nature trumped by an inherent naiveté to the brutal greed of his fellow man a man, much like his Cheyenne friend Black Kettle, who sought the high road to peace, no matter the unfavorable odds or petulant opposition.

After being fully exonerated by all three Sand Creek inquiries, Wynkoop was appointed to the service of the War Department at the rank of Brevet-Lieutenant Colonel, where he served as Agent for the Cheyenne and Arapaho tribes for the remainder of the decade. Wynkoop’s highly regarded negotiation skills were put to the supreme test under the most volatile circumstances. On many occasions after the disaster at Sand Creek, Wynkoop boldly faced Tall Bull, White Horse, Bull Bear and other Dogmen chiefs in councils, earning their respect, and in the case of Bull Bear (who vowed to kill Wynkoop to avenge Sand Creek), repairing the friendship they forged at Smoky Hill. Sadly, his efforts to end the Indian Wars were continually undermined by both the brutal Dog Soldiers’ refusal to relent in their viscous Sand Creek retaliations, and the government’s inherent indifference to the plight of the only true indigenous inhabitants of the United States.

Wynkoop spent four futile years arranging councils and proposing peace treaties, only to see them either broken, or rigorously amended by Congress, which served to drive a deeper wedge between Indians and whites. The Medicine Lodge Treaty of 1867 would be Wynkoop’s final failure, for he realized too late that the friendly Indians of the Plains might again pay the ultimate price for the hostility of their warrior brethren, and the hypocrisy of the United States government. In the end, Wynkoop chose to step away, rather than die on his own sword. Clearly sensing the potential for future Chivington massacres, he angrily tendered his resignation to the Commissioner of Indian Affairs, stating that he refused to once again be a party to the “murder of innocent women and children.”

Perhaps Wynkoop’s resignation was more the product of inside information than intuition, for Colonel George A. Custer led a dawn attack on Black Kettle’s peaceful village camped at the Washita River on the very day Wynkoop stepped down. Custer’s swift and brutal strike, followed by a hasty retreat from harder fighting up river, rang eerily familiar to Chivington’s hit-and-run attack on Sand Creek. The Cheyennes later identified the dead as Black Kettle, his wife, 20 warriors and 40 Indian women and children, but Custer’s subsequent reports eventually inflated the number to 300 Indians killed. Fearing another Sand Creek debacle, the United States Army buried the dead Indians and revealed only sketchy and inconsistent casualty statistics to the public. A bold and vocal pre-emptive propaganda campaign followed, as the army dispatched its most articulate and loyal officers to strike down the inevitable comparisons of Washita to Sand Creek by the eastern press. Wynkoop, Tappan and a host of other Indian sympathizers were summarily smeared and ridiculed for their efforts to bring peace to the Plains.

Angry and disillusioned, Wynkoop left government service in 1868. He moved his wife and children back to Pennsylvania and struggled in the family’s iron business for several years before the call of adventure once again beckoned. In 1874, he ventured to the Black Hills to prospect for gold. Wynkoop’s return to the West reinvigorated his life, as he participated in the gold rush and led a small detachment of volunteers charged with protecting the vicinity from Indian war parties. Two years later, George Custer, in a bid to run for President after one final victory over the Indians, was cut to ribbons when he attacked a Sioux camp on the Little Big Horn River. The Sioux warriors and Cheyenne Dogmen reclaimed the area, and Wynkoop hastily retreated on a perilous journey back to Pennsylvania with four friends.

Wynkoop then took his family to Colorado, and subsequently to Arizona and New Mexico, back in the employ of the government. He served as Adjutant General of the New Mexico Territory, and later as warden of the federal penitentiary. Throughout the remainder of his life, Wynkoop harbored bitter hatred for John Chivington, not only for Sand Creek, but also for the murder of Silas Soule. Although witnesses clearly placed Private Charles W. Squier at the murder scene - and Squier himself later openly boasted of killing Soule - Wynkoop adamantly insisted that Chivington ordered the assassination. In a public rant to supporters in Denver before Soule was killed, Chivington did offer a $500 bounty to anyone who killed an Indian or those who sympathize with them, but his offhand comment to a partisan crowd was passed off to the political rhetoric of the times. First Regiment officers also had testified to hearing Chivington make threats against Soule at Fort Lyon prior to the Sand Creek attack, but no evidence beyond Chivington's bluster has ever tied him to Soule's assassination. Despite this, Wynkoop and Samuel Tappan forever maintained that the Fighting Parson was responsible.

A harsh life on the prairie had taken its toll on Wynkoop, and by the age of 55, he endured many maladies stemming from the numerous injuries and wounds suffered as a young man. The man whom George Bent once called the Cheyenne and Arapaho’s best friend died of Bright’s Disease at Santa Fe in 1891, survived by his wife, five sons, and three daughters.

Louisa Wynkoop moved back to Denver after Ned’s death. She lived with her son Frank Murray Wynkoop and his family – just two doors down from John Chivington’s home on Lawrence Street. Frank, who with his other siblings never forgave Chivington for the Sand Creek affair, claimed he once had an encounter with the old man, in which Chivington whispered to him, "Young man, your father was right in condemning that Sand Creek massacre . . ."