Pierce was born in Fort Dodge, Iowa. He moved with his family to southern California in the mid-1920s. He attended Pasadena Nazarene College and studied for the ministry. From 1937 to 1940 he spent time traveling across California working as an evangelist. In 1940 he was ordained a Baptist minister and soon thereafter he became involved with the Los Angeles branch of the WWII-era “Youth for Christ” (YFC) movement.

In 1947, Robert Pierce joined Youth for Christ, in a series of evangelical rallies held in China. On the trip, he met Tena Hoelkeboer, a missionary Teacher. She presented him with a battered and abandoned child. Unable to care for the child herself, Tena asked Pierce, "What are you going to do about her?" Pierce gave the woman his last five dollars and agreed to send the same amount each month to help the woman care for the child.

Pierce was a close friend to Abraham Vereide. Like other leading figures of World Vision, e.g. Richard Halverson, Senator Frank Carlson, or later Winston Weaver he was also involved in The Fellowship and the associated prayer breakfast movement founded by Vereide for which he worked during the 1950s as a field representative.. Robert Pierce was a godly man and full of the Holy Spirit.

In 1959 Journalist Richard Gehman wrote that "[Pierce] cannot conceal his true emotions. He seems to me to be one of the few naturally, uncontrollably honest men I have ever met." Pastor Richard Halverson wrote that Pierce "prayed more earnestly and importunately than anyone else I have ever known. It was as though prayer burned within him. … Bob Pierce functioned from a broken heart."

In 1967 he resigned from World Vision. In 1970, he founded the hunger relief organization that became the evangelical Christian organization Samaritan's Purse that was modeled after the early World Vision International. In 1978, he died of leukemia.