Thousands of flights were grounded across the nation, with JetBlue cancelling one third of its Sunday flights.
Other major airlines with a smaller number of cancellations include Spirit, Southwest, American, Frontier, Alaska, and Allegiant.
In total, airlines canceled more than 3,500 U.S. flights this weekend and delayed thousands more, citing weather in Florida and other issues.
"Over the past several days, severe weather in the southeast and multiple air traffic control delay programs have created significant impacts on the industry," a JetBlue spokesperson said in a statement. "Today's cancellations will help us reset our operation and safely move our crews and aircraft back into position. We apologize to our customers for the inconvenience and we are working to get them on their way as quickly as possible."
The situation is leading to checked bags being separated from travelers, and the luggage is piling up.
In some cases, people are giving up on air travel and finding alternate options to get to their destinations.
One group of four cousins was supposed to fly from Nashville to Boston, but after cancellations and numerous delays, they opted to drive 17 hours home.
"We were kind of scrambling, obviously, to find other flights and everything and trying every which way to land in different cities or to try different airlines," Amanda Gately said. "But, I mean, all of the flights were just unavailable or they were like $1,500 for one way."
FlightAware, a website that tracks flights, noted major disruptions at several Florida airports, including in Miami, Ft. Lauderdale, Tampa and Orlando, as well as Baltimore, New York and other airports around the country.
The spate of cancellations arrived as air travel is rebounding from the pandemic, with strong demand for spring-break flights. People on social media complained about waiting on hold or in lines for hours to get their canceled flights rescheduled and being stranded for days.
Southwest Airlines also cited "weather and airspace congestion" Saturday in Florida, as well as a "technology issue." It canceled about 1,000 flights over the weekend.
American said Florida weather Saturday affected its operations, and it was recovering.
Alaska Airlines seemed to be dealing with a separate issue. The airline said Sunday that weekend flight cancellations that began Friday have affected more than 37,000 customers and, further cancellations were possible. The airline declined to say why it canceled flights, but referred in its statement to contract negotiations with its pilots. Off-duty pilots picketed in several U.S. cities Friday over stalled negotiations. They have been without a new contract for three years.
"Alaska Airlines failed to properly plan for increased travel demand and take the steps necessary to ensure it attracted and retained pilots," the pilots union said in a Friday press release.
(ABC News and the Associated Press contributed to this report)