This chapter examines the engagement of the People’s Republic of China (hereafter referred to as China) and the United States of America (USA) with the states in Central Asia in the era of the evolving Chinese Belt and Road Initiative (BRI). China has had the upper hand in dealings with the Central Asian states, both in bilateral relations and within the Shanghai Cooperation Organization (SCO). It has invested billions of dollars into infrastructure and manufacturing projects; however, it continues to disregard environmental and climate-related issues. China’s widely known repressive policies toward its Muslim populations and corruption negatively impact its engagements with Central Asia and could lead to an increase of anti-Chinese sentiments in the long term. The USA has had its strategy on Central Asia in place, but it has shown significant shortcomings. The latest US strategy seeks to empower the Central Asian states against other regional players, such as China. However, the US investments will depend on the goodwill of private investors who seek commercially viable and sustainable projects. The commitment of the USA is linked to the progress in reaching a peaceful resolution of the situation in Afghanistan, which has been the centerpiece of the US activities in the Greater Central Asia from the early days. The chapter argues that both countries will have to deliver more on promises and treat the Central Asian states as partners, while respecting the local governments and their multi-vectoral foreign policies. With the increased interest in connectivity and infrastructure projects from other countries, China and the USA are going to face an increasingly competitive strategic environment and, as such, must stay proactive if they wish to succeed in their initiatives and visions.