"[6] Yohannes followed his passion for protecting the environment through practical, sustainable methods by co-founding the New Resource Bank in San Francisco in 2006.

In September 2009, President Barack Obama nominated Yohannes to serve as CEO of the Millennium Challenge Corporation, a U.S. development agency that aims to reduce global poverty by investing in select countries that demonstrate a commitment to good governance.

[7] Upon his confirmation, Yohannes stated, "It is challenging to replace patronage with partnership and to deliver smart aid that matters by encouraging good policies, country-led development, and sustainable results.

"[7] Described by CNN as "Obama's man on global development,"[8] Yohannes brought his private sector expertise to the position, stating that, to bring the greatest returns to American taxpayers, MCC should be run effectively and efficiently, “just like a business.

"[4] Under Yohannes' leadership, MCC started or completed investments of more than $9 billion in 25 countries on projects that lifted more than 173 million people out of poverty.

Yohannes accompanied the president in Senegal from June 27–28 and in Tanzania from July 1–2, where the U.S. delegation announced the administration's Power Africa initiative, in which MCC plays a role.

"[11] Referring to MCC's work in Africa, Yohannes stated that, "in addition to helping many African partners become self sufficient...we're also creating the next markets for American products and services.

[1] As ambassador, Yohannes has established climate change, tax reform, governance, development, and inequality as top priorities for the United States at the OECD.

In July, he published a joint op-ed with OECD Secretary-General José Ángel Gurría, arguing that the United States can lead a global transition towards a more inclusive model of economic growth.

[18] In October, he created a Friends of Inclusive Growth group, then leveraged his role as chair to foster collaboration with local government and private sector leaders.

[20] Yohannes also led outreach to the private sector, hosting the launch of the OECD Initiative on Business and Inclusive Growth on November 15, 2016.

[27] A strong advocate for diversity, he argued that “in diplomacy as in every other area, America’s greatest resource is its difference.” In June 2016, Yohannes co-hosted the first-ever Ethiopian American Policy Briefing at the White House.

In his opening remarks, he told Ethiopian Americans that “America’s melting pot is a recipe for success” and that “what we make of our immigrant experience is up to us.”[28] Yohannes is active in his community and has served on various boards and civil organizations, including sitting on the board of Project C.U.R.E (Commission on Urgent Relief & Equipment), an organization that delivers donated medical supplies and equipment to more than 120 developing nations around the world, and the National Jewish Hospital.

Yohannes helped to fund the building of a new research and medical facility at the hospital, the Iris and Michael Smith Clinics and Laboratories, which opened in 2007.