"Any person joining Delta in the future we will mandate to get vaccinated before they can sign up with the company," Chief Executive Ed Bastian told CNN on Thursday evening.
And he said he would "strongly encourage" Delta's current 75,000 employees to get the vaccine, urging them to "understand the risk to not get vaccinated."
Staffers who decline vaccinations might face restrictions, such as not being able to work on overseas trips, Bastian said.
Over 60% of Delta workers have received at least one shot, and the airline believes about 80% will get fully vaccinated, he said.
Delta recently traded at $45.52, up 3.5%, in an up day for the market as a whole. The stock has gained 21% over the past six months amid investor optimism about vaccinations, economic recovery and a restart to travel.
Last month, Delta reported a wider-than-expected first-quarter loss but said it expected to return to profitability later this year.
"If recovery trends hold, we expect positive cash generation for the June quarter and see a path to return to profitability in the September quarter as the demand recovery progresses," Bastian said in a statement.
Delta posted an adjusted net loss of $3.55 a share, widening from a 51-cent per-share loss last year.
On May 1, Delta allowed travelers to return to the middle seats in its planes. The Atlanta carrier was the last U.S. airline to lift this restriction, which was put in place last April at the beginning of the coronavirus pandemic.