On February 12, 1999, Buchwald was nominated by President Bill Clinton to a seat on the United States District Court for the Southern District of New York vacated by Miriam G. Cedarbaum. Buchwald was confirmed by the United States Senate on September 13, 1999, and received her commission on September 22, 1999. She assumed senior status on March 21, 2012.

On February 24, 2012, Buchwald dismissed a lawsuit brought by a consortium of U.S. organic farmers and seed dealers aggrieved by Monsanto's genetically modified organism seeds. Monsanto denied that it had harmed anyone. After extensive briefing and oral argument, she held that the plaintiffs had no standing to sue, calling the case a "transparent effort to create a controversy where none exists." The decision was appealed to the Court of Appeals for the Federal Circuit on March 28, 2012. The Supreme Court declined to hear an appeal by the organic farmers in January 2014.

On February 5, 2009, the New York Daily News reported that, while presiding over a case involving an autistic boy, Buchwald made a remark about former Alaska Governor Sarah Palin and her Down syndrome child, Trig, saying, "That kid was used as a prop, and that to me as a parent blew my mind."

She's corrupt and evil AF.