President Donald Trump named Gottlieb, 46, to head the agency in March 2017 after he acted as deputy commissioner under former President George W. Bush. Gottlieb is leaving the administration in order to spend more time with his family in Connecticut.
"I'm immensely grateful for the opportunity to help lead this wonderful agency, for the support of my colleagues, for the public health goals we advanced together, and the strong support of [Health and Human Services Secretary Alex Azar] and [Trump] -- This has been a wonderful journey and parting is very hard," he tweeted.
Trump said Gottlieb did an "absolutely terrific job" heading the FDA.
"Scott has helped us to lower drug prices, get a record number of generic drugs approved and onto the market, and so many other things. He and his talents will be greatly missed!" the president tweeted.
Gottlieb, who previously had ties as an advocate for drug companies, has focused much of the past two years on combatting underage tobacco sales. Under his leadership, the FDA has particularly targeted companies that market e-cigarette devices to teens.
"We're seeing too many cases where companies are designing e-liquid products in packages that resemble children's food items and this sort of egregious marketing can lead to accidental ingestion of potentially lethal doses of nicotine by young kids," he said in a November warning to e-cigarette companies. "There's no excuse for this sort of packaging and we'll continue to target these products and the companies that market them."
Azar said he's proud of the work Gottlieb has done at the FDA.
"He has been an exemplary public health leader, aggressive advocate for American patients, and passionate promoter of innovation," he said. "I will personally miss working with Scott on the important goals we share, and I know that is true for so many other members of the HHS family."