In 2010, Cooley won the Republican nomination for California Attorney General against John C. Eastman and Tom Harman in the June 8 primary election.

During the general election campaign, Cooley said he would defend Proposition 8, a 2008 ballot measure that banned same-sex marriages in California but was then being appealed in the federal courts.

At his 2000 swearing-in ceremony, he charged his over 1,000 prosecutors – including more than 300 District Attorney investigators and 600 clerical, technical and support staff – to "show no fear in pursuing the criminal element, but also be fearless in the pursuit of justice."

Cooley changed the office's policy on California's Three Strikes Law, with the stated purpose to assure proportionality in sentencing and even-handed application countywide.

In eight out of eight cases, he opposed the use of a California law that allows battered women in prison to be given a new hearing if evidence of domestic violence was omitted during the original proceedings.

[14] Just a week before the 2008 election that he ultimately won, Cooley was attacked for violating Jessica's Law and making a deal with defense attorneys and judges to postpone seeking tougher sanctions against a group of serious sex offenders that had completed their prison terms.

[15] In June 2008, Cooley was elected to a third term, defeating his challengers, Steve Ipsen, President of the L.A. County Prosecutors Union, and Albert Robles, an attorney and professor.

Cooley told the L.A. Times, just before voters went to the polls over "Marsy's Law" that the measure, which ended up passing, would sweep aside "decades of legislative scrutiny and judicial review."

"[16] The L.A. Times editorial desk wrote on April 28, 2008, of Cooley, "It is noteworthy that he criticized predecessor Gil Garcetti in 2000 for seeking a third term and promised that he would serve only two."

[18] In October 2008, a jury found Robles not guilty of all charges after deliberating for only 20 minutes,[18][19] and he was re-elected a month later to his seat on the board of the Water Replenishment District of Southern California.

Judge Wright issued a preliminary injunction ordering Cooley to desist from behavior seen as discriminating and/or retaliating against employees on the basis of union membership.

Thomas S. Kerrigan, an L.A. County hearing officer for the Employee Relations Commission heard months of testimony and found that veteran deputy district attorneys and prosecutors under Cooley, with outstanding evaluations, were retaliated against.

[24] In 2009, Cooley gained coverage all over the country when, along with federal authorities, he requested that the Swiss government arrest and extradite movie director Roman Polanski, who was traveling to the Zurich Film Festival.

Polanski had been a fugitive for 31 years after originally fleeing the United States in February 1978 after pleading guilty to unlawful sex with a minor in Los Angeles.

[26] His administration aggressively prosecuted political corruption in the City of Los Angeles as well as such communities as Bell, Vernon, Beverly Hills, Compton, Inglewood, South Gate, Temple, and Irwindale among many others.

[32] On July 11, 2017, Judge Orrick found attorneys Cooley and Ferreira in contempt of court saying, "With respect to the criminal defense counsel, they do not get to decide whether they can violate the preliminary injunction".

[35][33] On August 31, Judge Orrick found Daleiden and his attorneys, Steve Cooley and Ferreira, liable for the payment of $195,359 to compensate the National Abortion Federation for legal fees and increased security for "expenses incurred as a result of the violation of my Preliminary Injunction Order".

Judge Orrick wrote that Daleiden's attorneys, Cooley and Ferreira, were included in the sanctions intended to ensure "current and future compliance" with his order.