Tillerson lobbied against Rule 1504 of the Dodd–Frank reform and protections, which would have required Exxon to disclose payments to foreign governments. In 2017, Congress voted to overturn Rule 1504 one hour before Tillerson was confirmed as Secretary of State.

Tillerson's tenure as Secretary of State lasted 405 days, one of the shortest tenures in modern history. Tillerson is the shortest-serving Secretary since Lawrence Eagleburger, who served during the last month of President George H. W. Bush's term. Excluding Secretaries whose tenures were ended by the arrival of a new presidential administration, Tillerson is the shortest-serving Secretary since 1900. According to long-time diplomat Aaron David Miller, Tillerson is also the only Secretary of State since at least 1945 to have been fired.

Tillerson was born on March 23, 1952, in Wichita Falls, Texas, the son of Patty Sue (née Patton) and Bobby Joe Tillerson, and named after Rex Allen and John Wayne, two Hollywood actors famous for playing Cowboys.

At age 14, he began to work as a bus boy in the student union building at Oklahoma State University. Two years later in 1968 he became a janitor working in one of the engineering buildings at the university. On weekends, he worked picking cotton.

Tillerson graduated from Huntsville High School in 1970. He was a section leader for the percussion section of his high school band, in which he played the kettle drums and snare drum, and he earned spots in the all-district and all-region bands during his senior year. Tillerson received a college scholarship from the University of Texas Longhorn Band. He received a Bachelor of Science degree in Civil Engineering from the University of Texas at Austin in 1975. During his time at UT Austin, he was involved with the Tejas Club, and the marching band.

Tillerson joined Exxon Company USA in 1975 as a production Engineer. In 1989, Tillerson became general manager of the central production division of Exxon USA. In 1995, he became President of Exxon Yemen Inc. and Esso Exploration and Production Khorat Inc.

Rex Tillerson has been married twice. He divorced his first wife, with whom he has twin boys. In 1986, Tillerson married Renda St. Clair, who has a son from her previous marriage. Tillerson also has a son, born in 1988, with St. Clair. Tillerson's twin sons are Engineers and hold their bachelor's degrees from the Cockrell School of Engineering at the University of Texas at Austin. In 2006, Tillerson was named a Distinguished Engineering Graduate.

In 1998, he became a vice President of Exxon Ventures (CIS) and President of Exxon Neftegas Limited with responsibility for Exxon's holdings in Russia and the Caspian Sea. He then entered Exxon into the Sakhalin-I consortium with Rosneft.

According to the Center for Responsive Politics, Tillerson has made tens of thousands of dollars of political donations to Republican groups and candidates. According to FEC records, he gave a total of $468,970 in contributions to Republican candidates and committees from 2000 to 2016.

Under Tillerson's leadership, ExxonMobil cooperated closely with Saudi Arabia, the world's largest oil exporter and a longtime U.S. ally; Qatar and the United Arab Emirates. From 2003 to 2005, a European subsidiary of ExxonMobil, Infineum, operated in the Middle East providing sales to Iran, Sudan and Syria. ExxonMobil stated that they followed all legal framework and that such sales were minuscule compared to their annual revenue of $371 billion at the time. In 2009, ExxonMobil acquired XTO Energy, a major natural gas Producer, for $31 billion in stock. Michael Corkery of the Wall Street Journal wrote that "Tillerson's legacy rides on the XTO Deal." Tillerson approved Exxon negotiating a multibillion-dollar deal with the government of Iraqi Kurdistan, despite opposition from President Barack Obama and Iraqi Prime Minister Nouri al-Maliki, both of whom argued it would increase regional instability.

Tillerson was a friend of Igor Sechin, the Executive Chairman of Rosneft, the Russian state oil company, and leader of the Kremlin's Siloviki (security/military) faction, who has been described as "Russia's second-most powerful person" after Putin. Exxon owns a dacha next door to Sechin's and Tillerson would often visit him there. Tillerson led Sechin on a tour of New York City, dining on caviar with him and Putin at the Per Se restaurant. In 2006, Exxon avoided making any government concessions in its Sakhalin-I oil field after Royal Dutch Shell was forced to sell half of its ownership in Sakhalin-II by the Russian government.

Speaking in March 2007 at a Council on Foreign Relations event, Tillerson said:

An article in The New York Times suggested that ExxonMobil's embrace of a carbon tax in October 2009 may have simply been an effort to avoid cap and trade legislation that was then being considered by the U.S. Congress as an alternative method of carbon pricing. A Time magazine article in December 2016 asserted that since Tillerson announced his company's preference for a carbon tax, ExxonMobil "has not made a carbon tax a focus of its massive lobbying efforts and has supported a number of candidates and organizations that oppose measures to tackle the climate change issue".

In 2010, Tillerson said that while he acknowledged that humans were affecting the climate through greenhouse gas emissions to some degree, it was not yet clear "to what extent and therefore what can you do about it".

In August 2011, Putin attended a ceremony in Sochi where Tillerson and Sechin signed an agreement between ExxonMobil and Rosneft to drill the East-Prinovozemelsky field in the Arctic Ocean valued at up to $300 billion. The Rosneft deal also gave the state-owned oil company a 30% stake in Exxon owned assets in the U.S. Gulf of Mexico, Canada, and West Texas. The company began drilling in the Kara Sea in the summer of 2014, and a round of sanctions against Russia introduced in September that year due to the Ukrainian crisis was to have brought the project to a halt in mid-September. Nevertheless, the company was granted a reprieve that stretched the window to work until October 10, which enabled it to discover a major field with about 750 million barrels of new oil for Russia. In July 2017, the U.S. Treasury's Office of Foreign Assets Control fined ExxonMobil $2 million for violating sanctions in its dealings with Sechin, leading the company to sue the government.

He is a Congregationalist who holds a membership in the National Association of Congregational Christian Churches, a mainline Reformed denomination. He and his wife donated between $5,000 and $10,000 to the denomination's The Congregationalist Magazine in 2012.

In September 2013, Tillerson wrote an op-ed piece in The Wall Street Journal defending Common Core.

On February 20, 2014, news outlets reported that Tillerson and his wife had joined opponents of a proposed water tower that could lead to fracking-related traffic near their homes. Plaintiffs included former U.S. House of Representatives Majority Leader Dick Armey and his wife. The Tillersons dropped out of the lawsuit after a judge dismissed their claim in November 2014.

In 2015, Tillerson was named as the 25th most powerful person in the world by Forbes.

In 2016, Tillerson stated, "The world is going to have to continue using fossil fuels, whether they like it or not."

In October 2017, Politico reported that Tillerson's major foreign policy positions include "urging the United States to stay in the Trans-Pacific Partnership and the Paris climate accord, taking a hard line on Russia, advocating negotiations and dialogue to defuse the mounting crisis with North Korea, advocating for continued U.S. adherence to the Iran nuclear deal, taking a neutral position in the dispute between Qatar and Saudi Arabia, and reassuring jittery allies, from South Korea and Japan to our NATO partners, that America still has their back".

Tillerson ended his tenure as Secretary of State on March 31, 2018.