Kudrow, who plays the ditzy Phoebe in NBC's "Friends," won best supporting actress in a comedy series.
"This isn't possible without you," Kudrow said after naming her co-stars in the comedy about a close-knit band of buddies in New York City.
It was Kudrow's first Emmy and increased NBC's early lead for the most trophies. The top-rated network had the most nominations and won 12 Emmys presented previously for creative arts.
Pierce was honored as best supporting actor in a comedy series for his role as high-strung, highbrow Dr. Niles Crane in NBC's "Frasier."
Pierce acknowledged fellow nominees and paid special tribute to "NewsRadio's" Phil Hartman, who was shot to death this year.
"You all know how great he is. I guess there's nothing else to say," Pierce said.
Hartman's mother, Doris, was in the audience.
Comedian Garry Shandling won his first Emmy, as a writer for "The Larry Sanders Show." Director Todd Holland also won an Emmy for his work on the critically praised show, which ended its run on HBO in May.
Emmys in 27 categories were to be presented by the Academy of Television Arts & Sciences in an expanded, four-hour anniversary show at the Shrine Auditorium south of downtown Los Angeles.
The ceremony acknowledged TV's history with salutes to figures both major and minor.
Among those taking bows were the host of "Mike Stokey's Pantomime Quiz," which received the first Emmy 50 years ago, and comedy titans Bob Hope, Milton Berle and Sid Caesar. A frail Hope was seated as the trio received a long-standing ovation.
NBC's "ER" and Fox's "The X-Files" were among the leading series nominees with 16 bids each. NBC's "Frasier" was the top comedy nominee with 11 nods, while Fox's "Ally McBeal" had 10 nominations.
The creator-producer of "Ally McBeal," David E. Kelley, took the unusual step of entering the hourlong show about a young attorney in a category that traditionally honors half-hour comedies.
"From the Earth to the Moon," HBO's 12-part, Tom Hanks-produced epic tale of the space program, was the most-nominated entry overall with 17 bids.
"Merlin," the special effects-laden NBC miniseries about the legendary magician who helped King Arthur rule, had 15 bids. It topped the list of programs honored at the earlier ceremony, winning four creative arts trophies.
NBC was the most-nominated network with 86, followed by HBO with 72. ABC had 54 bids, CBS received 36 and Fox had 35.
The Emmy ceremony swapped its home of two decades, the Pasadena Civic Auditorium, for the roomier Shrine this year. Audience capacity was doubled to about 6,000, making more tickets available to industry members and, for the first time, to the public.
Sunday's show had audiences in 92 foreign countries. Last year, the academy estimated a half-billion viewers in 90 countries.
In a non-televised ceremony on Aug. 29, awards in categories including outstanding choreography, editing and makeup were announced.
Besides the 12 trophies presented to NBC, eight each went to ABC and HBO. Fox won five and CBS won four.
Four acting awards for guest roles also were presented. They went to Mel Brooks for "Mad About You," Emma Thompson for "Ellen," Cloris Leachman for "Promised Land" and John Larroquette for "The Practice."
In the second year of the Emmy award for best commercial, Apple Computer Inc. received the trophy for its "Think Different" entry.