Graphic: 2016 Delegate Count and Primary Results

Mr. Romney, who was still duking it out in his own primary campaign, did not start airing ads in earnest until the fall. By then, he was well defined in the public’s eye.

“President Obama’s super PAC ran an ad that basically accused Mitt Romney of giving a woman cancer,” Mr. Williams said. “The ads were outrageous, offensive and widely panned by the media and fact checkers. But unfortunately, with several million dollars behind them, they were effective in damaging his image.”

The enduring potency of negative ads has helped the Republican candidates define opponents other than Mr. Trump. In December and January, a super PAC supporting Senator Marco Rubio of Florida took aim at Gov. Chris Christie of New Jersey as Mr. Christie was making a late push in New Hampshire. The ads, which painted Mr. Christie as corrupt and too close to Mr. Obama, took a toll, and Mr. Christie, who wound up finishing sixth in New Hampshire, was forced from the race.

Right to Rise also used its advertising budget to reinforce negative perceptions about Mr. Rubio, which, coupled with a poor debate performance, halted his early rise.

But in those cases, the targets were easier: Neither Mr. Rubio nor Mr. Christie was particularly well known at a granular level among voters, so new information helped shape voters’ perceptions. Mr. Trump is an established brand for many people, which means that damaging his reputation is likely to require a more concentrated effort.

To that end, Priorities USA — the super PAC supporting Mrs. Clinton, which also backed Mr. Obama in 2012 — has begun reserving $70 million in television ad time from the Democratic convention in late July through Election Day, air time that is almost certain to be dedicated to ravaging Mr. Trump if he is the nominee.

Steve Murphy, a veteran Democratic ad maker, said that Mr. Trump should view the primaries as a mere taste of what is to come.

“Ask Donald Trump if he thinks negative ads hurt him in Wisconsin,” Mr. Murphy said. “Then tell him the Democrats have another half a billion dollars’ worth ready to go in the general.”