More than 2 million middle and high school students were users of e-cigarettes in 2017, according to the agency. "So, now, I'm able to tell them, 'I no longer smoke cigarettes'".
Gottlieb called the action "historic" and said it was the largest coordinated enforcement effort in the agency's history.
Makers argue that e-cigarettes can help adult smokers transition away from burnt tobacco products.
Under Wednesday's announcement, the five largest e-cigarette manufacturers will have 60 days to produce plans to reverse underage use of their products.
Budding research on e-cigarettes also suggests that these flavors contain terpenes that may be more damaging to the lungs than other flavors are.
"We see clear signs that youth use of electronic cigarettes has reached an epidemic proportion", Gottlieb said. "It's now clear to me, that in closing the on-ramp to kids, we're going to have to narrow the off-ramp for adults who want to migrate off combustible tobacco and onto e-cigs".
Juul owns about 72 percent of the USA market for e-cigarette sales, according to Wells Fargo.
Gottlieb cited preliminary data that has not yet been published, but which he said shows "youth use of e-cigs is rising very sharply".
The FDA says it has issued "more than 1,300 warning letters and fines to retailers" as a result of "a large-scale, undercover nationwide blitz to crack down on the sale of e-cigarettes to minors".
"I have grown increasingly concerned around what we see as rising youth use in these products, and I'm disappointed in the actions the companies have taken to try to address this", Gottlieb said at a press briefing.
Other studies have indicated that while e-cigarettes may have milder effects on the lungs, they are just as bad - if not worse - for the cardiovascular system, raising risks of heart disease and high blood pressure. That initiative emerged from the agency's broader plan to regulate nicotine and tobacco, unveiled in July 2017, under the Family Smoking Prevention and Tobacco Control Act.
Several of the manufacturers targeted by the FDA - Juul, MarkTen, Vuse, Blu and Logic - issued statements agreeing with the need to limit access to minors and announcing their willingness to work with the FDA to reach a solution. To address the trend, the agency set a 60-day deadline for the five major tobacco manufacturers to provide a plan describing how they will address the widespread youth access and use of their products. As part of today's action, the agency sent an additional 12 warning letters to another 12 companies that continue to sell the products. As part of that plan, Gottlieb has suggested some smokers could be directed toward alternative products that deliver nicotine without the carcinogens of cigarettes.
The FDA is in the process of rolling out a sweeping anti-smoking initiative created to make it easier for smokers to quit by cutting the nicotine levels in regular cigarettes. The company has more than two-thirds of the USA e-cigarette market, according to Nielsen data.
"In my view, they treated these issues like a public relations challenge rather than seriously considering their legal obligations, the public health mandate, and the existential threat to these products".