[11] Following the outbreak of 2022 Kazakh unrest, President Kassym-Jomart Tokayev appointed Smaiylov as the acting prime minister of Kazakhstan on 5 January 2022, in response to the resignation of his predecessor Asqar Mamin and his government.

[12][13] According to Joanna Lillis from Eurasianet, Smaiylov along with other ministers is a technocrat with role in "carrying the baggage" of a "tainted cabinet" and that his appointment as the head of government would provide more clues in Tokayev's future policies.

[14] On 11 January 2022, the Mäjilis, the lower house of the Parliament of Kazakhstan, approved Smaiylov as the new prime minister with 89 deputies across party factions unanimously voting in favour for his candidacy.

[15] With 9 out of 20 total ministers being new appointees, the First Smaiylov Government faced tasks in improving the quality of life for citizens, maintaining economic growth, dealing with the ongoing COVID-19 pandemic, restoring the widescale damage and leading Kazakhstan out of the aftermath caused by the unrest.

[19][20] On 31 July 2023, Smaiylov signed a resolution to allocate an additional 918 million tenge from the government reserve for purchasing fire-fighting overalls for employees of forest fire stations working in environmental institutions and forestries.

[25] Amid rising COVID-19 cases in several regions of Kazakhstan, Smaiylov on 12 January 2022 instructed the Ministry of Healthcare and local executive bodies to increase PCR testing, monitor operations, ensure medical readiness, and prevent drug shortages, emphasizing the need for mobile medical teams to provide home care and free medicines, while also significantly increasing the rate of population revaccination under the personal control of regional akims.

[28] Smaiylov emphasized the plan's focus on increasing citizens' incomes and reducing youth unemployment, with strict oversight by state officials to ensure effective implementation.

[29] In March 2022, the Program to Increase Incomes of the Population until 2025 was adopted, aimed at improving citizens' well-being and updating social and labour policies by boosting employment in industry and entrepreneurship through the creation of new industrial clusters, financial support for small and medium-sized businesses (SMEs), and fostering SME development around large enterprises; in the agricultural sector, it includes measures to establish households, implement investment projects, and expand microcredit mechanisms, with the overall goal of reducing the share of the population earning below the subsistence level, reducing unemployment, and creating about 2 million new jobs by 2025.

[35] Facing an 8.1% inflation rate, Smaiylov instructed government bodies to take measures to increase food production, control trade markups, monitor pricing practices, and ensure market saturation.

Smaiylov attributed the cause to rising global food prices and urged state bodies and regional akims to strengthen efforts to curb inflation and take effective measures.