The money, intended for charitable missions, had been collected during four Christmas weekend services at Pendleton Center United Methodist Church.
An estimated 1,300 people attended the services, with most of them giving Christmas offerings.
"I'm basically in shock, and there's a sense of betrayal and disappointment," the Rev. Thomas M. Kraft told the Buffalo News.
"Our congregation is quite in shock."
The Niagara County Sheriff's Office was informed when church staff discovered the donations were missing early Monday.
Two interior doors were smashed in and another inside door was unlocked with a key or otherwise bypassed, Kraft said.
"There was definitely forced entry as a part of it," he said. "They broke through two interior doors and bypassed one locking system. They knew right what they were looking for."
Christmas giving is typically double or triple what the church gets from collections in a normal weekend, Kraft said.
"Evidently, someone was planning this. This wasn't a last-minute thought," he said. "It may be a total stranger, but more likely it's someone who's been in this building."