80 senators voted to back von Eschenbach, with 11 opposing.
Von Eschenbach, formerly the head of the National Cancer Institute, has been holding the position temporarily for more than a year - he was approved in September 2005 by the Senate Health, Education, Labour and Education Committee - but senators had stalled a final vote on his nomination.
The FDA has been without a permanent chief for nearly four-and-a-half of the last six years. During that time, the agency has faced several criticisms and has been under intense scrutiny.
The agency faces "increasingly complex scientific, medical and regulatory issues," said von Eschenbach in a statement.
"I am humbled by the responsibility with which I have been entrusted."
This official nomination comes at a crucial time especially with the uncertainties over the agency's budget for the review of new drug applications. The FDA and the pharmaceutical industry have been in strong negotiations to decide how much drug companies will pay the agency to review new drugs from the end of next year, when the current law expires.
Last month, the FDA's deputy commissioner Scott Gottlieb said that pharma companies should contribute additional funds so the agency can study the drugs' safety once they reach the market.
The US drug industry is now negotiating the fourth version of the Prescription Drug User Fee Act (PDUFA) with the regulator - the outcome could change radically the landscape for pharma companies.
Drug safety concerns intensified after Merck pulled arthritis pill Vioxx from the market two years ago when a study showed long-term use doubled the risk of heart attack and stroke.
In addition, a report on the FDA's drug approval process by the Institute of Medicine (IOM) published in September said that the agency needed more budget and manpower to ensure it keeps its focus on the safety of the drugs it regulates, not only before approval, but also throughout the time they are on the market.
"We found an imbalance in the regulatory attention and resources available before and after drug approval," said at the time Sheila Burke, chair of the committee.
"Staff and resources devoted to preapproval functions are substantially greater. Few high-quality studies are conducted after approval."
The FDA admitted that more needed to be done to ensure the safe and effective use of prescription drugs, however it pointed out that much progress and reform of its safety oversight enterprise was already under way.
The agency regulates food, medicine, medical devices and cosmetics with a budget of $1.88bn and more than 12,000 staff.
The pharmaceutical industry backed the Senate decision saying the agency needed a permanent leader.
"A permanent FDA commissioner speaks with greater authority about the resource needs of the FDA during the budgetary process and is more likely to be focused on long-term programs and policies," said Billy Tauzin, president of the Pharmaceutical Research and Manufacturers of America, an industry trade group, in a statement.
Von Eschenbach will have a lot on his plate in the next few months.